This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. More than one million adults are diagnosed annually with chronic brain diseases, disorders or injuries. Unfortunately, a majority of the therapies developed may only be administered by injecting them directly into the brain because the blood brain barrier (BBB), a tight seal of various cells, impedes delivery of most drugs. Nanoscience provides unique opportunities to address this issue. Dendrimers are highly customizable nanopolymers that appeal to biologists and chemists because of their precise architecture, size/shape control, high uniformity/purity, high loading capacity, low toxicity and low immunogenicity. These qualities also make them ideal for use in drug delivery. The purpose of this proposal is to design novel dendrimers that cross the BBB and to test their efficacy in doing so. Our hypothesis is that by modifying surface groups of generation 4 PAMAM and generation 3 Priostar" dendrimers with substances known to cross the BBB, we may create potential drug delivery vehicles that may use endogenous transporter mechanisms to gain entrance to the brain. In this study, we will synthesize Priostar" dendrimers with a biotin surface groups.